Reduced Elimination of Cyclosporine A in Elderly (>65 Years) Kidney Transplant Recipients

Background. Physiologic functions that may affect pharmacokinetics of drugs are altered in elderly patients. The current study was performed to elucidate the effect of age on cyclosporine A (CsA) pharmacokinetics in renal transplant recipients. Method. Twenty-five renal transplant recipients on CsA treatment were included in the Study. CsA doses were adjusted by C, monitoring. The patients were divided into two groups based on age; elderly: more than 65 years (n = 11, mean 73 years) and Younger: 18 to 64 years (n = 14, mean 43 years). A full 12-hr pharmacokinetic profile was performed during stable phase. CsA whole blood and intracellular T-lymphocytes concentrations (first 6 hr) were measured. Genotyping of the CYP3A5*1/*3 and ABC131 (C1236T, G2677T, C3435T) polymorphisms and quantification of whole blood mRNA ABC131 expression were performed in all patients. Results. Elderly patients achieved target C, levels with lower CsA doses than the younger patients (4.3 +/- 0.8 vs. 6.1 +/- 2.1 mg/day/kg, P=0.025) because of lower clearance of CsA (22.7 +/- 5.1 vs. 30.5 +/- 11.1 L/hr, P=0.031). Elderly patients also showed 44% higher intracellular-to-whole blood CsA ratio than younger patients (P=0.02). Neither the CYP3A5*1, the ABC131 genotypes nor mRNA ABCB1 expression revealed any significant influence on CsA pharmacokinetics. Conclusion. The clearance of CsA decreased with increasing age. In addition, elderly patients had a significant larger proportion of the whole blood CsA concentration located at the site of action (within T lymphocytes). This indicates that in elderly recipients it might be safe to aim for an even lower whole blood target levels than current guidelines propose.